PF3D7_0711000 (CDC48)

Genome location: Pf3D7_07_v3:486,497..491,719(-)

Genome classification: Core

Function and Localization

Product Description: AAA family ATPase, CDC48 subfamily

SignalP Peptide: N/A

# Transmembrane Domains: 1

EC Numbers: 3.6.4.6 (Vesicle-fusing ATPase)

Curated GO (PlasmoDB):

Type	GO Term	Name
Component	GO:0034098	VCP-NPL4-UFD1 AAA ATPase complex
Component	GO:0020011	apicoplast
Component	GO:0005737	cytoplasm
Component	GO:0005829	cytosol
Component	GO:0005634	nucleus
Function	GO:0016887	ATP hydrolysis activity
Function	GO:0031593	polyubiquitin modification-dependent protein binding
Function	GO:0043130	ubiquitin binding
Process	GO:0071712	ER-associated misfolded protein catabolic process
Process	GO:0097352	autophagosome maturation
Process	GO:0016236	macroautophagy
Process	GO:0051228	mitotic spindle disassembly
Process	GO:0010564	regulation of cell cycle process
Process	GO:0030970	retrograde protein transport, ER to cytosol
Process	GO:0030433	ubiquitin-dependent ERAD pathway

Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):

Stage	LR class	MCA mean	MCA prop. zeros
Sporozoite	expressed	N/A	N/A
Ring	expressed	0.69	0.69
Trophozoite	expressed	1.50	0.32
Schizont	expressed	0.24	0.87
Gametocyte	expressed	0.49	0.73

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0711000

Resistome Missense Mutations: D687N

Resistome Compounds with Missense Mutations: SQ109

Resistome # Samples with Disruptive Mutations: 2 (2 missense, 2 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.125 | MFS: -2.992 | #Insertions: 0

PlasmoGEM Phenotype: Insufficient data (Pb ortholog: PBANKA_1423200)

Relative Growth Rate: nan ± nan
Confidence: 0.10

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: P46468

"Best" AlphaFill ligand hit: ADP (adenosine-5'-diphosphate, Local RMSD=0.04) with 4KOD (Global RMSD=8.28)

BRENDA EC Inhibitors:

EC #	Name	EC Inhibitors
3.6.4.6	vesicle-fusing ATPase	BRENDA SOAP query unsuccessful

Orthology to BindingDB Entries:

UniProt	Protein Name	Species	Homology Source	BindingDB Ligands
P55072	Transitional endoplasmic reticulum ATPase		HOGENOM	Gossypol (C9)Hexach-loropheneMLS000566888cid_15944801...
Q01853	Transitional endoplasmic reticulum ATPase		HOGENOM	US9206129, 1US9206129, 2US9206129, 3US9206129, 4...

Orthology Information

Ortholog Group (OrthoMCL): OG6_102053

Most Similar Human Ortholog: O15381

TM-align score: 0.65 | RMSD: 4.27

Seq Identity: 0.40 | Length: 624 / 1229

All Human Orthologs (OrthoMCL):

Gene ID	Description
ENSG00000143748	nuclear VCP like

Protein Information

Protein Length: 1229 | Molecular Weight (kDa): 142.08

UniProt ID(s): P46468

PDB ID(s): None

Isoelectric Point: 9.48

Protein Domain Annotations:

Source	Family ID	Description
InterPro	IPR003338	CDC48, N-terminal subdomain
InterPro	IPR003593	AAA+ ATPase domain
InterPro	IPR003959	ATPase, AAA-type, core
InterPro	IPR003960	ATPase, AAA-type, conserved site
InterPro	IPR009010	Aspartate decarboxylase-like domain superfamily
InterPro	IPR027417	P-loop containing nucleoside triphosphate hydrolase
InterPro	IPR029067	CDC48 domain 2-like superfamily
InterPro	IPR041569	AAA ATPase, AAA+ lid domain
PFam	PF00004	ATPase, AAA-type, core
PFam	PF17862	AAA ATPase, AAA+ lid domain
Superfamily	SSF50692	Aspartate decarboxylase-like domain superfamily
Superfamily	SSF52540	P-loop containing nucleoside triphosphate hydrolase
Superfamily	SSF54585	CDC48 domain 2-like superfamily

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type	common	rare	doubleton	singleton
synonymous	16	52	21	87
disruptive	22	86	55	133
missense	18	69	49	112

Any inclusion in genotype call

variant type	common	rare	doubleton	singleton
synonymous	27	121	41	65
disruptive	63	247	121	331
missense	35	179	107	219

PlasmoDB Total SNPs: 104

Non-coding: 47 | Synonymous: 40 | Nonsynonymous: 17 | Stop Codon: 0

Associated Publications

PMID	Title	Authors	DOI/Link
12368864	Genome sequence of the human malaria parasite Plasmodium falciparum.	Gardner MJ, Hall N, ..., Barrell B	10.1038/nature01097
12368867	Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.	Hall N, Pain A, ..., Barrell BG	10.1038/nature01095
16267556	A protein interaction network of the malaria parasite Plasmodium falciparum.	LaCount DJ, Vignali M, ..., Hughes RE	10.1038/nature04104
19502583	An unusual ERAD-like complex is targeted to the apicoplast of Plasmodiumfalciparum.	Spork S, Hiss JA, ..., Przyborski JM	10.1128/EC.00083-09
30212465	Integrative proteomics and bioinformatic prediction enable a high-confidenceapicoplast proteome in malaria parasites.	Boucher MJ, Ghosh S, ..., Yeh E	10.1371/journal.pbio.2005895
37422133	Optogenetic control of Cdc48 for dynamic metabolic engineering in yeast	Bezold F, Scheffer J, ..., Taxis C	10.1016/j.ymben.2023.06.013
38187576	Bidirectional substrate shuttling between the 26S proteasome and the Cdc48 ATPase promotes protein degradation	Li H, Ji Z, ..., Rapoport TA	10.1101/2023.12.20.572403
38401542	Bidirectional substrate shuttling between the 26S proteasome and the Cdc48 ATPasepromotes protein degradation	Li H, Ji Z, ..., Rapoport TA	10.1016/j.molcel.2024.01.029
37643243	The E3/E4 ubiquitin ligase UFD-2 suppresses normal and oncogenic signalingmediated by a Raf ortholog in Caenorhabditis elegans	Townley R, Deniaud A, ..., de la Cova CC	10.1126/scisignal.abq4355